The three dimensional structure of proteins which play regulatory roles in the growth of normal and tumor cells is being investigated. These proteins are (1) nerve growth factor (NGF) - a small protein which regulates growth and development of the sympathetic and embryonic sensory nervous system, (2) epidermal growth factor (EGF) - a protein functionally related to NGF which regulates growth of epidermal cells, and (3) L-glutaminase-asparaginase (GLA) - from Acinetobacter, a tumor inhibitory protein. Our main objective is to understand the various interactions of the growth proteins and tumor-inhibitory protein (GLA) in order to learn more about their mechanism of action on a molecular level. These interactions include: precursors of the growth proteins (proNGF and proEGF) with the arginine esteropeptidase enzymes; the formation of the stable complexes containing both the latter enzyme and the active growth promoting subunit derived from the "pro" precursor; the interactions of this active subunit with its membrane bound receptor; and the interaction of GLA with its substrate. These interactions are known to be highly specific and a detailed knowledge of the three-dimensional structures is essential for understanding their nature. A further goal is the understanding of the structural and functional homology among the growth proteins - for example, NGF and insulin. NGF and GLA have been crystallized and the low resolution structure of NGF will soon be forthcoming. Study of the structure of all the proteins is continuing using electron microscopy and x-ray diffraction techniques. Crystal diffraction is also being studied using synchrotron radiation. Because of the high intensity and "tuneability" of this unconventional source, the study of smaller crystals and phasing by use of anomalous scattering techniques appear to be very feasible. A computer controlled four-circle diffractometer and monochromator system for data collection on protein crystals has been developed and is available for use by outside groups.